We propose to investigate possible direct effects of LHRH agonists on the testes and the prostate in rats. While it is widely thought that LHRH agonist treatment alters gonadal function by altering pituitary hormone secretion, our recent data show that some of these effects can be obtained by hypophysectomized animals, suggesting that LHRH agonists act directly on extrapituitary tissue. The present project will expand these observations. The proposed project will: (1) Determine if large doses of agonist decrease and small doese increase the number and/or association constant (Ka) of testicular prolactin (PRL) and follicle stimulating hormone (FSH) and prostatic androgen and PRL receptors. We have recently domonstrated such biphasic effects of LHRH agonist, D-Trp 6-LHRH on testicular LH/hCG receptor in hypophysectomized rats. If similar effects are demonstrated for other hormone receptors, the result may indicate that LHRH agonist affects a common step(s) in receptors turn-over process. (2) Determine if effects on a given receptor population occur independently of effects by other hormones which also alter the receptor. (3) Ascertain if changes in gonadal peptide hormone receptors are associated with alteration in steroidogenesis. (4) Determine if the observed effects are specific to LHRH agonist. (5) Determine if high affinity LHRH binders exist in the testes and prostate and how agonist treatment affects these binders. (6) Determine the time and extent of agonist-induced morphological changes at the light and electron microscope level. (7) Determine, using cell culture, if agonist treatment alters steroidogenesis, protein synthesis or lysosome activity. (8) Explore possible relationships between agonists treatment and cyclic nucleotides. (9) Assess the physiological significance of agonist-induced effect; determine if LHRH-like substance(s) exists in testes and other tissue. The results obtained in these studies will provide much important information in physiology of extrapituitary action of LHRH agonists.